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Addressing the controversy: do bisphosphonates directly affect primary tumors?
Sterling JA
(2015) Cancer Discov 5: 14-5
MeSH Terms: Animals, Bone Density Conservation Agents, Diphosphonates, Female, Humans, Macrophages, Neoplasms, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed
Show Abstract · Added February 12, 2015
The recent article by Junankar and colleagues focuses on demonstrating the uptake of bisphosphonates (BP) into the primary tumor in both animal models and human samples. Interestingly, the authors were able to establish tumor-associated macrophages as the cell type that takes up the BPs. These studies are an important advancement for understanding the potential benefits of using BPs as adjuvant therapy in patients with cancer.
©2015 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
9 MeSH Terms
Detection of breast cancer microcalcification using (99m)Tc-MDP SPECT or Osteosense 750EX FMT imaging.
Felix DD, Gore JC, Yankeelov TE, Peterson TE, Barnes S, Whisenant J, Weis J, Shoukouhi S, Virostko J, Nickels M, McIntyre JO, Sanders M, Abramson V, Tantawy MN
(2015) Nucl Med Biol 42: 269-73
MeSH Terms: Animals, Bone and Bones, Breast Neoplasms, Calcinosis, Cell Line, Tumor, Humans, Mice, Optical Imaging, Technetium Tc 99m Medronate, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed
Show Abstract · Added January 20, 2015
BACKGROUND - In previous work, we demonstrated the presence of hydroxyapetite (type II microcalcification), HAP, in triple negative MDA-MB-231 breast cancer cells. We used (18)F-NaF to detect these types of cancers in mouse models as the free fluorine, (18)F(-), binds to HAP similar to bone uptake. In this work, we investigate other bone targeting agents and techniques including (99m)Tc-MDP SPECT and Osteosense 750EX FMT imaging as alternatives for breast cancer diagnosis via targeting HAP within the tumor microenvironment.
METHODS - Thirteen mice were injected subcutaneously in the right flank with 10(6) MDA-MB-231 cells. When the tumor size reached ~0.6 cm(3), mice (n=9) were injected with ~37 MBq of (99m)Tc-MDP intravenously and then imaged one hour later in a NanoSPECT/CT or injected intravenously with 4 nmol/g of Osetosense 750EX and imaged 24 hours later in an FMT (n=4). The imaging probe concentration in the tumor was compared to that of muscle. Following SPECT imaging, the tumors were harvested, sectioned into 10 μm slices, and underwent autoradiography or von Kossa staining to correlate (99m)Tc-MDP binding with HAP distribution within the tumor. The SPECT images were normalized to the injected dose and regions-of-interest (ROIs) were drawn around bone, tumor, and muscle to obtain the radiotracer concentration in these regions in units of percent injected dose per unit volume. ROIs were drawn around bone and tumor in the FMT images as no FMT signal was observed in normal muscle.
RESULTS - Uptake of (99m)Tc-MDP was observed in the bone and tumor with little or no uptake in the muscle with concentrations of 11.34±1.46 (mean±SD), 2.22±0.95, and 0.05±0.04%ID/cc, respectively. Uptake of Osteosense 750EX was also observed in the bone and tumor with concentrations of 0.35±0.07 (mean±SD) and 0.04±0.01picomoles, respectively. No FMT signal was observed in the normal muscle. There was no significant difference in the bone-to-tumor ratio between the two modalities (5.1±2.3 for SPECT and 8.8±2.2 for FMT) indicating that there is little difference in tumor uptake between these two agents.
CONCLUSION - This study provides evidence of the accessibility of HAP within the breast tumor microenvironment as an in vivo imaging target for bone-seeking agents. SPECT imaging using (99m)Tc-MDP can be rapidly translated to the clinic. FMT imaging using Osteosense 750EX is not currently approved for clinical use and is limited to animal research.
Copyright © 2014 Elsevier Inc. All rights reserved.
0 Communities
5 Members
0 Resources
11 MeSH Terms
Phospholipid ether analogs for the detection of colorectal tumors.
Deming DA, Maher ME, Leystra AA, Grudzinski JP, Clipson L, Albrecht DM, Washington MK, Matkowskyj KA, Hall LT, Lubner SJ, Weichert JP, Halberg RB
(2014) PLoS One 9: e109668
MeSH Terms: Adenocarcinoma, Animals, Colorectal Neoplasms, Female, Humans, Indoles, Intestinal Neoplasms, Iodobenzenes, Lymphatic Metastasis, Mice, Neoplasm Invasiveness, Phospholipid Ethers, Phosphorylcholine, Tomography, Emission-Computed, Single-Photon
Show Abstract · Added April 12, 2016
The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×10(10) vs 3.27×10(9) respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.
0 Communities
1 Members
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14 MeSH Terms
Quantitative multimodality imaging in cancer research and therapy.
Yankeelov TE, Abramson RG, Quarles CC
(2014) Nat Rev Clin Oncol 11: 670-80
MeSH Terms: Biomedical Research, Humans, Image Processing, Computer-Assisted, Multimodal Imaging, Neoplasms, Positron-Emission Tomography, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Translational Medical Research
Show Abstract · Added February 12, 2015
Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein.
0 Communities
2 Members
0 Resources
9 MeSH Terms
Missense dopamine transporter mutations associate with adult parkinsonism and ADHD.
Hansen FH, Skjørringe T, Yasmeen S, Arends NV, Sahai MA, Erreger K, Andreassen TF, Holy M, Hamilton PJ, Neergheen V, Karlsborg M, Newman AH, Pope S, Heales SJ, Friberg L, Law I, Pinborg LH, Sitte HH, Loland C, Shi L, Weinstein H, Galli A, Hjermind LE, Møller LB, Gether U
(2014) J Clin Invest 124: 3107-20
MeSH Terms: Adult, Amino Acid Sequence, Amino Acid Substitution, Animals, Attention Deficit Disorder with Hyperactivity, Brain, Cohort Studies, DNA Mutational Analysis, Dopamine, Dopamine Plasma Membrane Transport Proteins, Female, HEK293 Cells, Humans, Male, Models, Molecular, Molecular Sequence Data, Mutant Proteins, Mutation, Missense, Oocytes, Parkinsonian Disorders, Pedigree, Positron-Emission Tomography, Protein Conformation, Recombinant Proteins, Sequence Homology, Amino Acid, Sodium, Tomography, Emission-Computed, Single-Photon, Xenopus
Show Abstract · Added February 19, 2015
Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.
0 Communities
1 Members
0 Resources
28 MeSH Terms
Importance of SPECT/CT images in a case to differentiate a chest wall soft tissue infection from pneumonia on 111In-tagged WBC scintigraphy.
Bhojwani N, Hartman J, Mehta L
(2014) Clin Nucl Med 39: 561-3
MeSH Terms: Diagnosis, Differential, Humans, Indium Radioisotopes, Leukocyte Count, Male, Middle Aged, Multimodal Imaging, Pneumonia, Soft Tissue Infections, Thoracic Wall, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed
Show Abstract · Added January 1, 2016
A 52-year-old man presented to the emergency department with a 3-day history of fevers and left flank pain radiating to the chest and neck. Total WBC count was 20,000/uL. Abdominal CT demonstrated small bibasilar pleural effusions. Because of persistent leukocytosis, an In WBC scintigram was ordered 5 days after admission, which demonstrated thoracic WBC accumulation on the planar images that localized to the left posterior chest wall on SPECT/CT. SPECT/CT may differentiate intrathoracic versus extrathoracic disease.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Safety and feasibility of adjunctive regadenoson injection at peak exercise during exercise myocardial perfusion imaging: The Both Exercise and Regadenoson Stress Test (BERST) trial.
Ross MI, Wu E, Wilkins JT, Gupta D, Shen S, Aulwes D, Montero K, Holly TA
(2013) J Nucl Cardiol 20: 197-204
MeSH Terms: Adenosine A2 Receptor Agonists, Adult, Coronary Artery Disease, Exercise Test, Female, Humans, Image Enhancement, Male, Myocardial Perfusion Imaging, Physical Endurance, Physical Exertion, Purines, Pyrazoles, Reproducibility of Results, Sensitivity and Specificity, Tomography, Emission-Computed, Single-Photon, Vasodilator Agents
Show Abstract · Added February 28, 2014
BACKGROUND - The data existing in the literature regarding the safety of using regadenoson with symptom-limited exercise are limited, which motivated the authors to undertake this randomized study.
METHODS - We offered patients scheduled to undergo vasodilator stress nuclear myocardial perfusion imaging the opportunity to exercise instead. Patients who failed to reach target heart rate (THR) were randomized to (1) receive regadenoson at peak exercise or (2) stop exercise and receive regadenoson at rest. Patients who reached THR received a standard Tc-99m sestamibi injection with no regadenoson.
RESULTS - 200 patients were included (66% male, mean age 52.5 ± 13.6). 125 patients (62%) reached THR with exercise alone. All stress protocols were well tolerated, and there were no significant adverse events. There were no statistically significant differences in the extent of perfusion abnormalities, image quality, or rate of referral to cardiac catheterization within 60 days between the groups. In fully adjusted logistic regression models, beta-blocker use and diabetes remained significant univariate predictors of failure to reach THR (OR 0.21, 95% CI 0.1-0.5, P < .0001, OR 0.34, 95% CI 0.2-0.7, P = .004, respectively).
CONCLUSIONS - A protocol combining regadenoson at peak exercise in patients unable to reach THR with exercise is feasible, well-tolerated, and yields comparable imaging results to a standard regadenoson injection at rest. In addition, pharmacologic stress testing may be over-ordered in current clinical practice, as patients referred for such testing were often able to exercise.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy.
Tantawy MN, Jiang R, Wang F, Takahashi K, Peterson TE, Zemel D, Hao CM, Fujita H, Harris RC, Quarles CC, Takahashi T
(2012) BMC Nephrol 13: 168
MeSH Terms: Animals, Kidney, Male, Mice, Mice, Inbred C57BL, Radioisotope Renography, Radionuclide Imaging, Radiopharmaceuticals, Technetium Tc 99m Mertiatide, Tomography, Emission-Computed, Single-Photon, Ureteral Obstruction
Show Abstract · Added August 27, 2013
BACKGROUND - Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease.
METHODS - UUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys.
RESULTS - Compared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney's peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period.
CONCLUSIONS - Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.
1 Communities
5 Members
0 Resources
11 MeSH Terms
Comparison of dynamic contrast-enhanced MRI and quantitative SPECT in a rat glioma model.
Skinner JT, Yankeelov TE, Peterson TE, Does MD
(2012) Contrast Media Mol Imaging 7: 494-500
MeSH Terms: Algorithms, Animals, Brain Neoplasms, Cell Line, Tumor, Contrast Media, Female, Glioma, Magnetic Resonance Imaging, Neoplasm Transplantation, Radiography, Rats, Rats, Sprague-Dawley, Tomography, Emission-Computed, Single-Photon
Show Abstract · Added November 13, 2013
Pharmacokinetic modeling of dynamic contrast-enhanced (DCE) MRI data provides measures of the extracellular-extravascular volume fraction (v(e) ) and the volume transfer constant (K(trans) ) in a given tissue. These parameter estimates may be biased, however, by confounding issues such as contrast agent and tissue water dynamics, or assumptions of vascularization and perfusion made by the commonly used model. In contrast to MRI, radiotracer imaging with SPECT is insensitive to water dynamics. A quantitative dual-isotope SPECT technique was developed to obtain an estimate of v(e) in a rat glioma model for comparison with the corresponding estimates obtained using DCE-MRI with a vascular input function and reference region model. Both DCE-MRI methods produced consistently larger estimates of v(e) in comparison to the SPECT estimates, and several experimental sources were postulated to contribute to these differences.
Copyright © 2012 John Wiley & Sons, Ltd.
0 Communities
3 Members
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13 MeSH Terms
Preface to the special issue on quantitative imaging in cancer.
Yankeelov TE, Gore JC
(2012) Magn Reson Imaging 30: 1201-2
MeSH Terms: Diagnostic Imaging, Fluorodeoxyglucose F18, Humans, Medical Oncology, Neoplasms, Positron-Emission Tomography, Tomography, Emission-Computed, Single-Photon
Added November 13, 2013
0 Communities
2 Members
0 Resources
7 MeSH Terms